This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This study is the second of the series of three studies on Unexplained Encephalitis Due to Possible Infectious Causes conducted in collaboration with State Health Departments of California, Tennessee and New York. This series of studies of unexplained encephalitis has been initiated to describe the epidemiology of encephalitis in selected areas of the United States;to characterize the etiologic spectrum of acute encephalitides in the United States;to identify the proportion of encephalitis cases with unexplained etiology;and decrease the proportion of unexplained cases of encephalitis by: developing improved diagnostic strategies, evaluating and implementing newly developed diagnostic tests for agents associated with encephalitis, and identifying new pathogens associated with encephalitis. A secondary goal of the study is to explore long-term neurocognitive outcomes among patients with encephalitis, and identify prognostic features. The study strategies comprise enhanced surveillance for encephalitis cases in study areas;extensive laboratory testing of identified cases, and creating a bank of clinical specimens for future testing as new etiologic agents are discovered. Patients will be referred to the study by their physicians. After patients or their families agree to be contacted, TUES personnel will obtain consent and assent. Participants will then undergo core diagnostic testing for common causes of encephalitis, and, if the results of core testing are negative, their specimens will be further tested for rare and newly identified agents. The left over specimens will be stored to be tested in the future as new pathogens associated with encephalitis are identified. Expected outcomes of the project are reports on the epidemiology of unexplained encephalitis;etiologic spectrum of encephalitides at study sites, as well as on clinical characteristics and risk-factors for encephalitides caused by different pathogens and testing algorithm for encephalitis aimed at minimizing the proportion of unexplained cases. The results of the study will be published in peer-reviewed journals and presented at the scientific meetings. Although the overall objectives, strategies and methods are similar for all three studies, the study protocols have been adapted to reflect established existing practices, local interests, differences in legal/IRB requirements, availability of resources at each of the participating sites and are therefore being submitted for the CDC IRB to review separately for each state. Main differences across study sites lie in the approaches to and procedures of data collection, obtaining informed consent, and applying slightly expanded case-definitions which enables them to recruit patient groups of special local interest. Nevertheless, the study protocol in each instance allows us to identify a core group of patients meeting standard clinical criteria and use comparable testing strategies across study sites.